Fetal intestinal lactase activity is extremely low prior to 32 - 34 wk gestation but appears to rise rapidly thereafter. Breath H2 concentration and the rate of whole body acetate production are high in preterm infants 32-36 wk post-conceptional age suggesting that lactose is largely fermented in the colon, but studies of growth and lactose tolerance imply that lactose hydrolysis is more efficient in post-natal life than predicted from these indirect indices of fermentation activity. During the last year of the present grant, a dual stable tracer technique was used to estimate a coefficient of in vivo lactose digestion (hydrolysis) in preterm infants 33-34 wk post-conceptional age. Based on the initial values (range: 0.8 - 1.2), it is hypothesized that lactose digestion is efficient (> 0.8) in preterm infants > 32 wk post- conceptional age (Aim 3). The Principal Hypotheses of this proposal address lactose digestion in preterm infants less than 32 wk post- conceptional age: (1) The coefficient of hydrolysis of lactose is < 0.80 and is dependent on the lactose intake. (2) At the lactose intakes normally ingested by such infants, the rate of entry into the circulation of lactose-derived glucose is insufficient to suppress (via insulin secretion) hepatic glucose output. To address these hypotheses, four Primary Specific Aims (Experiments) are proposed: (1) To define the reliability of the dual stable tracer technique for estimating lactose digestion in 5 preterm infants less than 32 wk post-conceptional age. (2) In 10 preterm infants less than 32 wk post-conceptional age: to define a point estimate for lactose digestion; to assess the effect of doubling the lactose intake on lactose digestion; to estimate the contribution of lactose-derived glucose and galactose to the systemic rate of appearance of glucose; and, using the above data, to assess hepatic glucose output. (3) By studying 5 additional infants, to complete the definition of a point estimate of lactose digestion in preterm infants > 32 wk post-conceptional age. (4) To define a point estimate of lactose digestion in 5 preterm infants less than 32 wk post- conceptional age fed human milk. The Secondary Aim is to determine the relationship of the lactose digestibility coefficient to the rate of breath H2 excretion (measured using a newly developed flow-through system). This study may be important to understanding the metabolism of lactose in preterm infants and should have relevance to the further development of feeding strategies which minimize formula intolerance and the risk of necrotizing enterocolitis especially in premature infants born prior to 30 wk gestational age.